Immunologic Research

, Volume 55, Issue 1–3, pp 210–216 | Cite as

TLR7 drives accumulation of ABCs and autoantibody production in autoimmune-prone mice

Immunology in Colorado

Abstract

Although autoantibodies are the hallmarks of most autoimmune diseases, the mechanisms by which autoreactive B cells are generated and accumulate are still poorly understood. Overexpression of Toll-like receptor 7 (TLR7) that recognizes single-stranded RNAs has been implicated in systemic lupus erythematosus (SLE), although the cellular mechanism by which this receptor drives the disease is unknown. We recently identified a population of CD11c+ age-associated B cells (ABCs) which is driven by TLR7 signaling, secretes autoantibodies and appears in autoimmune-prone mice by the time of onset of autoimmunity. Mice lacking the Mer receptor develop autoantibodies and splenomegaly similar to other mouse models of SLE. Here, we show that Mer−/− mice that lack TLR7 fail to develop anti-chromatin IgG antibodies, perhaps because they also fail to develop ABCs. Moreover, depletion of CD11c+ ABCs from Mer−/− mice leads to rapid reduction in autoantibodies. Together, these data strongly suggest that ABCs and/or their descendants are the primary source of autoantibodies in Mer−/− mice and that TLR7 signaling is crucial for accumulation of ABCs and development of autoantibodies. These data demonstrate for the first time that TLR7, and not TLR9, is responsible for generation of anti-chromatin IgG antibodies in Mer−/− mice.

Keywords

Mer receptor tyrosine kinase Age-associated B cells Toll-like receptor 7 Autoantibodies 

Notes

Acknowledgments

The authors thank Ms. D. Garcia and Drs. T. Detanico, M. Phillips and M. Munks for assistance. This work was supported in part by USPHS AI-18785, AI-22295, AI-52225 and AI-046374 and Colorado Bioscience Discovery Evaluation Grant Program (#11BGF-20).

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Integrated Department of Immunology, Howard Hughes Medical InstituteUniversity of Colorado School of MedicineDenverUSA
  2. 2.Integrated Department of Immunology, National Jewish HealthUniversity of Colorado School of MedicineDenverUSA
  3. 3.Department of PharmacologyUniversity of Colorado Health Sciences CenterAuroraUSA
  4. 4.Department of MedicineUniversity of Colorado Health Sciences Center, DenverAuroraUSA
  5. 5.Department of Biochemistry and Molecular GeneticsUniversity of Colorado Health Sciences CenterAuroraUSA

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